Project Summary: Over 780,000 strokes occur annually in the U.S. with at least 125,000 directly related to intracranial atherosclerosis (ICAD). Despite the important consequences of ICAD, its prevalence remains unclear. Traditional ICAD diagnosis has depended on stenosis measured by angiography; however, in other vascular beds, lumen narrowing is a poor indicator of plaque burden when vessels accommodate plaques by remodeling. The ability to detect and characterize plaque in vivo without relying on lumen assessment has recently been shown in extracranial plaque using high-resolution MRI. We propose to develop high-resolution MRI techniques to characterize the unique features of ICAD. This will be implemented in an NIH-funded population-based study, the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), to investigate ICAD prevalence in the US and factors that lead to its development and stroke. In the K99 training phase of this grant, I will be supervised by an outstanding team of mentors with expertise in neuroradiology, neurology, pathology, MRI physics and epidemiology. Training will be conducted via course work, mentored research, and progress reviews. The major objective of my mentored research is to determine ICAD prevalence, and examine ICAD stenosis and burden in relation to risk factors and vascular markers. In the independent phase (R00), I will apply knowledge gained from the first grant period (K99) to characterize ICAD plaque components and determine associations of these components with ischemic stroke. My overall hypothesis is that high- resolution MRI vessel wall and plaque imaging will improve our ability to stratify stroke risk, thereby enabling new strategies for primary stroke prevention and treatment. The training environment at Johns Hopkins is especially well-suited for this research since it offers access to state-of-the art instrumentation and an infrastructure with a long track-record of supporting clinical research. Relevance: New MRI methodologies for characterizing intracranial atherosclerotic plaque morphology and composition will stratify risk for ischemic events and lesion progression. Information obtained from high resolution MRI of atherosclerosis can be valuable in refining strategies for primary stroke prevention and treatment.